Good day, and thank you for standing by. Welcome to the Vertex Pharmaceuticals VX-147 phase II results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone. Please be advised that today's conference is being recorded. If you're requiring further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Michael Partridge, Senior Vice President of Investor Relations. Please go ahead. Good morning. We look forward to discussing with you today our APOL1 program and our VX-147 phase II results. On the call making prepared remarks we have Dr. Reshma Kewalramani, Vertex's CEO and President, and Dr. David Altshuler, Vertex's Chief Scientific Officer. We recommend that you access the webcast slides as you listen to this call. These slides provide context for understanding the role of APOL1 in kidney disease and also depict the phase II data in more detail. This call is being recorded. A replay will be available on our website. We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission. These statements, including without limitation, those regarding Vertex's plans to advance VX-147 into pivotal studies, including the anticipated timing of these studies, our expectations for our VX-147 program, including next steps and potential accelerated regulatory approval, and other programs in our pipeline, are based on management's current assumptions. These forward-looking statements represent the company's beliefs only as of the date of this call. Actual outcomes and events could differ materially. We undertake no obligation to update or revise these statements. I will now turn the call over to Dr. Reshma Kewalramani. Thanks, Michael. Today marks an important milestone in our understanding of APOL1 as not just a causal genetic factor in kidney disease, but as a therapeutic mechanism by which the disease course can be attenuated and thereby transform the lives of patients with kidney disease. It's my pleasure to review our phase II proof of concept results for VX-147 and our plans to advance this molecule into pivotal development. Before I do that, I'll turn the call over to David to provide some context for this program and these results. David? Thanks, Reshma. APOL1 is one of the most important human genetic discoveries of the last 15 years. An exceptional case in which a common genetic variant is a major driver of a serious disease that currently lacks effective treatment. The mutations in APOL1 are found in people with recent African ancestry and contribute substantially to the increased prevalence and severity of kidney disease in this population. Six years ago, we started our internal APOL1 program. We formed an exclusive partnership with Martin Pollak and David Friedman, who discovered the role of APOL1 in kidney disease. We built the assays, know-how needed to discover compounds targeting APOL1, all with the goal of making medicines that could address the underlying genetic cause of severe kidney disease. As Reshma will show when she describes the phase II results, the understanding we developed around APOL1 biology, the assays we created, and the compounds we discovered are now proving themselves in the clinic. Here's what we've come to understand. The common mutations in APOL1 encode a toxic gain-of-function protein that, when triggered by an infection or other insult, damages kidney cells called podocytes. Podocytes are key to the integrity of the filtration barrier in the kidney. When these podocytes are damaged, this leads directly to protein leakage in the urine, called proteinuria, and progression to end-stage renal disease requiring dialysis or transplant. Natural history studies show that patients with kidney disease who have APOL1 mutations progress much more quickly to kidney failure than other patients. Podocyte injury driven by APOL1 is the root cause in a group of kidney disease patients that have more typically been described according to clinical and histological presentation. The discovery of APOL1 turned this understanding on its head, moving from diagnosis based on histology, for example, FSGS, or comorbidity, for example, hypertension, to a precision medicine approach where diagnosis is grounded in the genetic basis of disease. Based on this genetic discovery, we now refer to these diseases as APOL1-mediated kidney disease or AMKD, which includes the subset with APOL1-mediated FSGS. This shift in APOL1 kidney disease is analogous to the shift that occurred previously in cancer, where oncologists moved from treating tumors based on their site of anatomical origin and histology to treatment defined by the underlying genetics. That is, when a tumor is positive for mutation of BCR-ABL or a mutation in the EGF receptor, it can be treated with a targeted therapy. Based on our new understanding of APOL1, we set out to discover drugs that block the disease-causing activity of the APOL1 protein. Specifically, we discovered compounds that directly bind to the APOL1 protein, inhibit the function of APOL1 in vitro, and protect against the relevant damage in human cells and in a mouse model engineered to carry the human toxic gain-of-function mutation. Some of these preclinical data were presented in November at the American Society of Nephrology annual meeting. We did all this work inside of Vertex, just as we did in CF, because we believe that the best way to create lasting clinical and commercial value is to validate and drug a new target with the development of proprietary assays, know-how, and chemical IP as far ahead of others in the field as is possible. With VX-147, we're now well on our way to advancing a targeted treatment for APOL1-mediated kidney disease, and I'll now turn it back to Reshma to review the clinical results. Thanks, David. The phase II study we're reporting today evaluated VX-147 in a patient population with biopsy-proven FSGS, two APOL1 variants, and proteinuria. The primary efficacy endpoint was reduction in proteinuria. The study also assessed safety and tolerability. We chose to do this first study of VX-147 in APOL1-mediated FSGS because this is a homogeneous, heavy proteinuria, and particularly aggressive form of APOL1-mediated kidney disease, or AMKD, for which there are no approved therapies and where patients unfortunately progress to end-stage renal disease rapidly. Demonstrating proof of concept in the severe patient population gives us high confidence of the mechanism and the magnitude of the treatment effect for all 100,000 patients with AMKD. The efficacy endpoint of reduction in proteinuria was measured as the% change from baseline to week 13. Safety, tolerability, and plasma PK were measured as secondary endpoints. VX-147 was dosed on top of standard of care medicines that patients may have been receiving for their kidney disease. ACE inhibitors, angiotensin receptor blockers, low stable doses of steroids and/or immunosuppressants were all allowed therapies. In the trial, VX-147 was dosed at 15 mg once daily for the first two weeks and then escalated to 45 mg once daily. A total of 16 patients were enrolled. At the end of 13 weeks of dosing, 13 patients were evaluable for the primary endpoint. Three patients were noncompliant with treatment and were therefore, per the pre-specified statistical analysis plan, excluded from the primary analysis. For the 13 evaluable patients, the mean age was 39, and the baseline urine protein was 2.21 grams per gram. Reductions in proteinuria were seen early within the first few weeks of treatment and continued through week 13. At 13 weeks, patients receiving VX-147 showed significantly reduced proteinuria, a mean reduction from baseline of 47.6%. An important finding given the association between proteinuria and progression of kidney disease. This serves as a clear indicator that inhibition of APOL1 is a powerful mechanism that holds the potential to slow the progression of kidney disease. Importantly, whether the patient had nephrotic or sub-nephrotic levels of proteinuria at baseline, the observed reduction on treatment were highly similar. This gives us further confidence that as we progress into the broader AMKD population with varying degrees of proteinuria, we can achieve substantial clinical efficacy. As you can see on slide 13, virtually all patients achieved significant reductions in proteinuria. Some patients had reductions of more than 70%. As discussed, 13 patients were evaluable for the pre-specified primary analysis. Nevertheless, we also conducted a sensitivity analysis that included all enrolled 16 patients. When we did that, the outcome and conclusions of the study are unchanged. The mean proteinuria reduction was 44%. Speaking as a nephrologist who has treated many patients with kidney disease, I'd like to contextualize a few key aspects of the 147 efficacy data set. First, proteinuria is a really important real-time clinical measure. In the management of patients with proteinuria kidney disease, the therapeutic goal is reduction in proteinuria. The greater the reduction, the better because decreases in proteinuria are highly correlated with slowing the progression to end-stage renal disease or ESRD. Second, I'd like to highlight that there are no approved treatments for AMKD that target the underlying cause of disease. The results we're seeing with VX-147 are on top of standard of care. In other words, the almost 50% reduction in proteinuria was seen in patients who were already taking ACE inhibitors or ARBs and/or steroids or immunosuppressants. From a safety perspective, VX-147 was well tolerated. No SAEs were considered related to VX-147, and all AEs were mild or moderate in severity. With these data in hand, we're working with urgency to advance the VX-147 program into pivotal development for the 100,000+ patients with APOL1-mediated kidney disease. The important next step is to conduct our end of phase II meeting with regulators, which we expect to complete in the near term, with the goal of initiating the pivotal development program in Q1 2022. I wanna take a minute to thank the study sites and patients who participated in our phase II trial. We are enormously grateful to the investigators, patients, and their families. In summary, VX-147 has demonstrated unprecedented, rapid, and robust reductions in proteinuria and was generally well-tolerated. Based on these results, we have an opportunity to transform the treatment of AMKD, which represents at least 100,000 patients and is a multibillion-dollar opportunity. We look forward to initiating the pivotal program for VX-147 in Q1 2022. Finally, I'd like to conclude by emphasizing that beyond its significance for AMKD, the clinical success of the VX-147 program provides important further validation for our differentiated R&D strategy, which is fundamentally based on our learnings from CF. As you know, in this strategy, we seek to develop transformative medicines for serious diseases by targeting causal human biology. We focus on developing predictive assays and using biomarkers in early clinical development that have high fidelity from bench to bedside. We pursue this strategy because we believe it significantly increases the odds of R&D success. The product that results from the strategy represents high-value medicines in specialty-driven markets. This strategy is delivering a pipeline of transformative medicines in CF, in sickle cell disease and beta thalassemia, in type 1 diabetes, and now in AMKD with VX-147. With that, let me open the call to questions. Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Michael Yee with Jefferies. Your line is open. Hey, good morning and congrats on the data. I know Reshma is a trained nephrologist. You could appreciate this. We had two questions related to that. One is, can you comment on the importance of eGFR and what you could show or what you need to show or what you'd like to show over time and what time course you think that would need to happen? Maybe talk about that a bit. Then second, I know you plan to start a pivotal, although you're still meeting with the FDA soon. Can you just reaffirm your confidence that proteinuria will be a primary endpoint and you do strongly believe you will get an accelerated approval on that if you could replicate this? Thank you. Yeah. Hey, Michael. Thanks for the kind words. As a nephrologist, these results are particularly exciting. With regard to eGFR, as I described in my prepared remarks, there is a known correlation between proteinuria and the progression to kidney disease. That progression to kidney disease is measured by decline in GFR, going on to dialysis or getting a transplant. In this phase II study of 13 weeks duration, the primary efficacy endpoint is proteinuria, and that's the 48% reduction in proteinuria that we see. It takes longer to see changes in GFR, and I would say we would expect to see changes somewhere beyond six months, maybe six months, nine months, 12 months, something like that. 13 weeks is too short to see changes in GFR. With regard to proteinuria as the regulatory enabling endpoint, you're right. We have started our conversations with regulators, but we have not yet had our end-of-phase II meeting. Regulators, particularly in the U.S., have expressed openness to proteinuria being a potentially regulatorily acceptable endpoint, especially for accelerated approval in homogeneous kidney diseases. Clearly from the description that David provided, I think it's becoming more and more clear that what we're talking about when we call this disease APOL1-mediated kidney disease is a genetically defined homogeneous proteinuria condition. Our goal is indeed to complete our discussions with the regulators and to seek a pathway to accelerated approval based on proteinuria. Got it. Thank you. Thank you. Our next question comes from Colin Bristow with UBS. Your line is open. Hey, good morning and congrats on the data. Just wanted to understand the AE profile a little bit better. I know it's a relatively short treatment period, but could you speak to the cadence of the adverse events, and did they tend to occur earlier, or did they build over time with treatment? Then just secondly, you know, one of the more common AEs was back pain. Do you have any more color here? Was this deemed musculoskeletal, or was this more flank pain and so anatomically could be considered more, you know, kidney-related? Thanks. Yeah. Hey, Colin. Sure thing. On the AEs, you know, this is a remarkably clean profile. Look, this is our phase II proof of concept study, and it's 13 weeks in duration, and we enrolled 16 patients. This is a remarkably clean profile. What we see here is no discontinuations due to AEs, no SAEs that are related to VX-147, and all AEs were mild to moderate. This is a really good-looking benefit risk profile. That's great. Could you speak to the cadence at all? No particular pattern, nothing that would lead you to believe it's early, middle or late. These are very mild to moderate AEs. No cadence. No, nothing there to share. Looks good. Okay. Presumably the back pain was more postural musculoskeletal. Is that a fair assessment? Yeah. You know, Colin, I would say these are the AEs that we're looking at are headache, nausea, back pain, sort of your garden variety AEs. Okay. Okay, that's great. Again, congrats on the data. Thanks so much, Colin. Thank you. Our next comes from Debjit Chattopadhyay with Guggenheim Partners. Your line is open. Hey, good morning, and thank you for taking the questions. I've got two. Could you talk to the underlying hypertension in these patients and if that was quantified pre and post-treatment? And number two, if proteinuria reduction was in the teens as opposed to 46% as reported, does that change the picture on the likely primary endpoint that is surrogate versus month nine eGFR for the pivotal study? Thank you. Debjit, I think you had two questions, one about blood pressure and one about maybe the magnitude of the treatment and effect on proteinuria. Let's take them in that order. Yes, that's right. Okay, super. With regard to blood pressure, we did assess blood pressure at baseline and at week 13. These patients, remember, were on a whole variety of standard of care medicines. Not only medicines like ACEs and ARBs, but also antihypertensive medicines. We don't see a change from baseline in blood pressure levels, from baseline to week 13. As I said, these patients are well treated for their blood pressure. Over time, Debjit, as kidney disease improves, you often see improvements in blood pressure. Of course, this is a 13-week study. With regard to the magnitude of the treatment effect, the 47.6% improvement in proteinuria bodes well in terms of the, let's call it, the hard renal endpoint, which is usually a composite of decline in GFR, going on to dialysis or transplantation. Because the natural history of studies, and when you look at protein-reducing studies, what they tell you is that the greater the decline in proteinuria, the better the hard outcome. This finding certainly bodes well for the hard outcome. Thanks for that. What I was trying to get at is, since you're getting such a large decrease in proteinuria, could you use that as a surrogate in the phase pivotal studies as opposed to using month 9 GFR changes if the proteinuria reductions were more marginal? Thank you. Yeah, yeah. Debjit, yes, that is correct. Our goal here is to complete our discussions with regulators and to look at proteinuria as the surrogate endpoint. Thank you so much. Yeah. Our next question comes from Robyn Karnauskas with Truist Securities. Your line is open. Hi, guys. Thanks for taking my question, and congrats on the data. I guess two questions I have. First of all, in things like KOL, they talked a lot about in the future they're going to be combining with maybe ETAs, the different mechanisms of drugs to get people to real normal levels of proteinuria. Can you talk a little bit about your thoughts on 'cause that would, you know, maybe get people to normal and maybe keeping people on drugs longer. Thoughts on after you get your pivotal trial started, potential combinations. For the broader opportunity, can you talk about maybe the near-term opportunities you might think about going into and how challenging they might be versus the more narrow indication you went to that's, you know, such a homogenous group of patients? Just give us a little bit of color on timelines and opportunities there. Thanks. Yeah, yeah. Thanks, Robyn. Let me start with the opportunity. There are at least 100,000 people with two APOL1 alleles, proteinuria, and kidney disease. That is almost certainly an underestimate of the opportunity because as you know, in rare diseases, when we don't have a therapeutic approach, it is difficult for patients and physicians to go through the process of diagnosis and especially genotyping if there is nothing for us to offer. I do think that this estimate of about 100,000 will grow as diagnosis and genetic diagnosis becomes more common. We are already working on that with patient groups and with physician groups, and so I think that that will improve. With regard to the studies and the regulatory pathway to the broad AMKD population and maybe how I see the results from the phase II study translating to AMKD, I have high confidence that the phase II results in the FSGS population will indeed be recapitulated in the broader AMKD population. The reason that I say that is threefold. The first is what David described in his prepared remarks. The disease, the underlying genetic disease is the same. What we see in FSGS, I expect to see in the broader population. Second, the FSGS population is a group of patients we intentionally studied in phase II. We intentionally studied this severe group of patients with high proteinuria and heavy pretreatment because we reasoned that when you study this in a severe population and if we see a high treatment effect, that we can then expand that to the broader population. Again, hearkening back to oncology and trials there when you study a molecule in a severe disease population and then use it in a broader population. The third reason I have high confidence is simply the magnitude of the treatment effect, which is large. Great. Next question comes from Brian Abrahams with RBC Capital Markets. Your line is open. Good morning. Thanks for taking my questions and congratulations on the data. Two from me. First off, I want to drill down on predictors of activity here. I'm just curious if you saw any correlation of PK to activity, and also whether you looked at G1 versus G2 risk alleles. I know VX-147 binds to both, but I think we've only seen G2 animal data so far. Secondarily, I'm curious if you could expand on how a pivotal for APOL1, a pivotal APOL1 basket study, could look. Might there be different regulatory requirements for the more versus less severe AMKD patients? Will additional dose ranging work be incorporated or required in a potential pivotal? Thanks. Yeah. Sure thing. Brian, let me ask David to comment on G1, G2 first, and then I'll come back with PK and what the phase III study could look like. No, thank you for the questions. The predictors of activity in our study were proteinuria and two APOL1 alleles. As you know, G1 and G2 have the same effect, same association to disease in the population, and we saw the same response regardless of genotype. I would point you to the slide in the prepared remarks that shows you, or in the press release, that shows you the waterfall plot, because what you can see is the consistency of the response across patients treated. The simple answer is it doesn't matter if it's G1, G2, it's anyone with proteinuria and two alleles in this population. We saw no other predictors of response. Brian, with regard to PK, we achieved our targeted PK across the board. With regard to what the pivotal trial might look like, as I mentioned in my prepared remarks, we have started the conversations with regulators, but we have not yet had our end-of-phase II meeting. Whether the study has a subgroup of subnephrotic range proteinuria and nephrotic range proteinuria like we did in phase II, or we simply target a certain number of patients in these two categories, the overall sample size and endpoint, et cetera, those are all the details we're gonna confirm with the agency at our end-of-phase II meeting. What I would say is, because of the way we designed our phase II study, that is to say, we pursued the more severe patient population. We specifically studied both nephrotic and subnephrotic range proteinuria patients, and we allowed baseline ACEs, ARBs, immunosuppressants, steroids. I feel very good about our ability to proceed to pivotal development in the broad AMKD population. Got it. Any additional dose ranging you'll need to do or want to do? Oh, yeah. Right. You know, I foresee us doing an adaptive phase II/III design and whether we use that a little bit of that adaptive to do some dose ranging is TBD. Clearly, 45 milligrams works. It's safe, and it's effective from our phase II program. Thanks, and congrats again. Yeah, thank you. Thanks, Brian. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Hi, everyone. Thanks for taking the question. This is Andrea on for Salveen. Reshma, maybe one question here on your portfolio strategy and this idea of continuing to study follow-up APOL1 inhibitors. Is there any particular profile that you're looking for that differs from VX-147? Thanks so much. Yeah. Hey, thanks for the question. I couldn't be more pleased with the results from the VX-147 phase II proof of concept study. We have a strategy in our research organization to pursue multiple molecules in parallel. As you've seen in CF and frankly, across our portfolio, that has served us very well. I'll turn it over to David to give you a sense for why we do that. No, thank you for the question. We continue to make new molecules behind our first always, because as I said in my opening remarks, our goal is to create lasting and durable clinical and commercial value by not only being first in class, but also being best in class. You see with KALYDECO, ORKAMBI, SYMDEKO, TRIKAFTA, and now VX-121, VX-561 triple, that strategy playing out and leading to that durable advantage. The thing about the APOL1 program that's so exciting for us is we are the only people in the clinic in patients with an APOL1 inhibitor. We're the only ones with this approach, and we already have multiple molecules in the clinic beyond this, and they have structural diversity, and they have some additional characteristics. It may be hard to outdo VX-147 because of the excellent initial profile, but we're not going to let that deter us because what we're looking for is to treat not just a small number of patients now, but a very large number of patients who can benefit from this medicine far into the future. Maybe a simple way of saying it, Andrea, is while it may be very, very difficult to out-innovate VX-147, if anyone does it, we'd like it to be us. Thank you. Our next question comes from Jason with Bank of America. Your line is open. Good morning. This is Jason on for Jeff. Congratulations on the data, and thank you so much for taking our questions. Two, if I may. Regarding the three individuals who were non-compliant, any color on what happened there, and do you think that's going to be an issue when we move to the next phase III? You kinda answered this question, but I'm thinking a little bit more broadly in terms of the overall indication scope of 147. You know, given APOL1's role in lupus nephritis or reducing longevity of transplanted kidneys, any broader indications that you're starting to think about now? Thank you. Yeah. See, thanks, Jason. With regard to the three patients that were non-compliant, no, nothing that concerns me there. We had a pre-specified statistical analysis plan that required compliance of a certain percent to be evaluated. I'll give you, for example, in the three patients. One patient developed COVID as an example. The AE profile, which I think is an important thing to know, is the following. No patients discontinued because of an AE. As I said before, no related to VX-147 SAEs, and all AEs were mild to moderate. When you have patients who may not complete the trial, the concern is around AEs and that is not a concern here. With regard to your other question about market opportunities, it's a very interesting question. The 100,000 patients that I referenced are 100,000 patients that have two APOL1 alleles that have proteinuria and let's call it a primary kidney disease. That's to say there's not another known etiology like the ones you mentioned, for example, lupus. We are indeed evaluating what the overall opportunity could be even amongst those who have another diagnosis. It's, for example, it is possible that patients who have two APOL1 alleles and lupus nephritis, and there's some emerging data to suggest this is the case, might also benefit from a drug like VX-147 that targets APOL1. Great question, and yes, we are investigating it, and those patients would be beyond the 100,000 I've referenced. Gotcha. Thank you so much for the color. Congratulations again on the data. Thank you. Our next question comes to Umer Raffat with Evercore ISI. Your line is open. Hi, this is Jingming on for Lisa. Congrats on the data. I have two questions. First is, how long has the patient been on a stable standard of care regimen before starting the VX-147 treatment? My second question is, could you give us some more color on what happened to that one patient whose proteinuria increased 25%? Yeah. Sure thing. I think, but I'll have Michael get back to you. I think the requirement to enter the phase II study was at least 28 days of stable medications. I'll have Michael confirm and get back to you on that. With regard to the individual patient plots of proteinuria, what I find really remarkable is that with the exception of one patient, everyone responded. That's unusual. We've obviously looked at that one patient to see if we can glean something and there's nothing that we can find there. I think the actual important finding is the remarkable effect on all patients except that one. That's right. I can't remember a time other than TRIKAFTA where you've seen waterfall plots in any medicine where pretty much everyone responds. That's interesting, David. Yeah. Yeah. Excellent. Thank you. Thank you. Our next question comes from Phil Nadeau with Cowen and Company. Your line is open. Good morning. Let us add our congratulations on the data. A few questions from us. First, as you think about doing the pivotal trial in the broader patient population, how do you think about powering the trial for proteinuria endpoint? Quantitatively, would you expect a 47.6% reduction in the FSGS population to predict a 47.6% reduction in the broader population? That's the first question. Second, kind of related, what does a 47% reduction in proteinuria mean for progression? How much would it delay kidney failure or death? The last question is on the 100,000 patients that you mentioned. What is the geographic distribution of those patients? What proportion are in the U.S. versus overseas? Thank you. Yeah. Let's take it in reverse order, Phil. The geographic distribution of the 100,000 patients that I referenced, those are the ones with two APOL1 alleles, proteinuria, and kidney disease that is not in association with another kidney diagnosis, right? That's that limited 100,000 patient population. It's 80% U.S., 20% in Europe. You ask some really great questions about proteinuria in the broader population and what can we infer from reductions in proteinuria to the hard renal endpoint. Let's start with proteinuria. I do expect that this—let's round it to 50%. I do expect that this almost 50% reduction in proteinuria in the FSGS population will translate to the broader AMKD population, and that's because of the three lines of reasoning that I had outlined previously. The first, that the genetic underpinnings of whether we call the disease FSGS or we call the disease AMKD is exactly the same. It's two APOL1 alleles that's leading to this condition. The second is that we intentionally studied this more severe population so that we had confidence when we went to the broader population of AMKD. Third, the simple magnitude of the treatment effect. Now, how do we translate proteinuria to the hard endpoint? This is a little bit more of a complicated question, but if you look at the totality of the evidence out there, including in diabetic and nondiabetic kidney disease or proteinuria kidney disease as a whole, the greater the reduction in proteinuria, the better the hard renal outcomes. What I would say is, and you've heard me say this before, we were looking for a double-digit decrease in proteinuria, but the higher the better, and this result bodes very well for the hard renal endpoint. David, do you have something you wanna add to that? Yeah, just one other thing I would remind people, and actually it's in a slide that we showed, is that in people with APOL1 mutations who have proteinuria, the outcomes are worse. They have more rapid progression and more severe disease. When you think about our result of 48% and think about it compared to others, just realize this is in a group of people who have a more severe, rapidly progressive disease, and that all the people we're gonna be studying share that gain-of-function mutation that our drug directly interacts with. I think that should give you confidence both of the magnitude of the effect and also why it will translate to others who have the same proteinuria and two copies of APOL1. Thanks, David. Thank you for Thanks, Phil. Congratulations on the data. Thanks, Phil. Operator, we have time for one more question. Our last question is from Alethia Young with Cantor Fitzgerald. Your line is open. Hi, this is Emily on for Alethia. Thanks for squeezing us in, and congrats on the positive data. Yes, I'm curious, is there a level of proteinuria that you would be looking to achieve that might be considered ideal in the FSGS population? I guess, for example, with lupus nephritis, that level is around 0.5. I'm curious if it's kind of similar here or how you're thinking about that. Thank you. Yeah, sure thing. Honestly, the higher the better. The greater the reduction in proteinuria, the greater the expectation for the hard endpoint, which is really what this is all about, right? What we are trying to do here is to prevent patients from going on to dialysis or needing a transplantation. All of the available evidence tells us that the greater the reduction in proteinuria, the better the likelihood of us being able to reduce the progression to end-stage renal disease. That's what we're looking for, the greatest magnitude of proteinuria reduction. This level is impressive. Okay, I think we are at the end of our time together. Thank you very much for joining the call, and we look forward to updating you on the progress of the VX-147 program, along with the rest of the pipeline in the coming months. Thank you. I'll just add, thanks, everybody for joining the call and the webcast this morning. The investor relations team is in the office if you'd like to follow up on the data. We certainly look forward to speaking with you. Have a great day. This concludes today's conference call. Thank you for participating. You may now disconnect.